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Follicular lymphoma

Follicular lymphoma is the most common slow-growing lymphoma. Most people live many years with it, treated only when it causes problems; it can be controlled repeatedly but rarely cured, and a minority transform into an aggressive lymphoma.

Follicular lymphoma (FL) is an indolent germinal-centre B-cell lymphoma defined by t(14;18) BCL2 overexpression in ~85% and frequent CREBBP, KMT2D and EZH2 mutations. Median survival now exceeds 15-20 years, so the questions are when to treat, how to avoid over-treatment, and how to manage the ~20% who progress within 24 months (POD24) and the 2-3% per year who transform to DLBCL.

Asymptomatic low-burden disease is watched or given rituximab monotherapy; symptomatic or high-burden disease receives anti-CD20 (rituximab or obinutuzumab) with bendamustine, CHOP or CVP, or with lenalidomide (R², RELEVANCE), usually followed by anti-CD20 maintenance (PRIMA). Relapsed disease has the richest menu in lymphoma: lenalidomide-rituximab (AUGMENT), CD20×CD3 bispecifics (mosunetuzumab 2022, epcoritamab 2024, odronextamab EU), CD19 CAR-T (axicabtagene 2021, tisagenlecleucel 2022, lisocabtagene 2024), zanubrutinib-obinutuzumab (ROSEWOOD, 2024) and radioimmunotherapy historically. Tazemetostat (EZH2) was withdrawn worldwide in March 2026.

Open questions: whether bispecifics or CAR-T should move to second line or even first line (EPCORE FL-1, MorningSun), PET/ctDNA-guided de-escalation, and biology-based prediction of POD24 and transformation.

State of the art today

  • Chemotherapy-free options now exist at every line: R² first line, bispecifics and BTK-anti-CD20 combinations at relapse.
  • CAR-T gives durable remissions in heavily pretreated FL (ZUMA-5 ~50% progression-free at 4 years) and is being tested against bispecifics.
  • POD24 identifies the high-risk fifth; how to treat them differently up front is still unknown.
  • Trials of bispecific plus lenalidomide first line (EPCORE FL-2, CELESTIMO) will decide whether chemotherapy leaves front-line FL.
Who it affects

Follicular lymphoma is the second most common non-Hodgkin lymphoma in the West (~20% of NHL; about 3-4 per 100,000 per year), median age ~65.

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Limited stage (I-II)

Involved-site radiotherapy 24 Gy (FoRT); rituximab alone or observation in selected cases.

NCCN · Category 1 (ISRT)
RituximabIMRT / IGRT (modern external beam)
Advanced, low burden, asymptomatic

Watch and wait (no survival penalty), or rituximab monotherapy to delay chemotherapy.

RituximabActive surveillance
Advanced, high burden (GELF criteria)

Bendamustine-rituximab or bendamustine-obinutuzumab (GALLIUM), R-CHOP, or lenalidomide-rituximab (RELEVANCE); anti-CD20 maintenance 2 years (PRIMA).

NCCN · Category 1ESMO-MCBS · 3 (GALLIUM)
RituximabObinutuzumabBendamustineLenalidomide
Relapsed (≥2 lines)

Lenalidomide-rituximab (AUGMENT); CD20×CD3 bispecific (mosunetuzumab, epcoritamab); CD19 CAR-T (axi-cel, tisa-cel, liso-cel); zanubrutinib + obinutuzumab; clinical trials.

NCCN · Category 2A
MosunetuzumabEpcoritamabAxicabtagene ciloleucelTisagenlecleucelLisocabtagene maraleucelZanubrutinibOdronextamab

Subtypes & biomarkers

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Subtypes
Biomarkers clinicians test
  • t (14;18)/BCL2
  • FLIPI / FLIPI2 / m7-FLIPI
  • PET-CT (Lugano) staging and end-of-induction response
  • POD24 (progression within 24 months)
  • EZH2 mutation
  • ctDNA (investigational MRD)

Target prevalence in this cancer

History

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  1. 1984t(14;18) links BCL2 to follicular lymphoma

    Tsujimoto and Croce clone the breakpoint; BCL2 becomes the first anti-apoptotic oncogene.

    BCL-2
  2. 1997Rituximab approved

    First monoclonal antibody for cancer, in relapsed indolent lymphoma.

    Rituximab
  3. 2004FLIPI prognostic index
  4. 2011PRIMA: rituximab maintenance

    Two years of maintenance doubles PFS after chemo-immunotherapy.

    Rituximab
  5. 2017Obinutuzumab first line (GALLIUM)
    Obinutuzumab
  6. 2018RELEVANCE: chemo-free R²

    Lenalidomide-rituximab matches chemo-immunotherapy first line.

    Lenalidomide
  7. 2021CAR-T enters FL

    Axicabtagene (ZUMA-5) approved; tisagenlecleucel (ELARA) 2022; lisocabtagene 2024.

    Axicabtagene ciloleucelTisagenlecleucelLisocabtagene maraleucel
  8. 2022First bispecific: mosunetuzumab

    Off-the-shelf CD20×CD3 with ~60% CR in third line.

    Mosunetuzumab
  9. 2024Epcoritamab and zanubrutinib-obinutuzumab approved for relapsed FL
    EpcoritamabZanubrutinib
  10. 2026Tazemetostat withdrawn worldwide

    Secondary haematologic malignancies; EZH2 leaves the FL armamentarium.

    Tazemetostat

Pipeline

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ApprovedBispecific T-cell engager (CD20×CD3)
Epcoritamab · Epkinly
ApprovedBispecific T-cell engager (CD20×CD3)
Mosunetuzumab · Lunsumio
ApprovedBispecific T-cell engager (CD20×CD3)
Odronextamab · Lynozyfic (EU: Ordspono)
Phase 3Molecular glue degrader (CELMoD, IKZF1/3)
Golcadomide
ApprovedCAR-T (CD19, defined CD4:CD8)
Lisocabtagene maraleucel · Breyanzi

Open problems

  • Transformation to DLBCL cannot be predicted or prevented.
  • Sequencing bispecifics vs CAR-T.
  • Whether earlier intensive therapy for POD24 patients improves survival.
  • Late toxicities of decades of therapy (secondary cancers, infections, immunoglobulin loss).

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Follicular lymphoma
condition: Follicular lymphoma
Open on ClinicalTrials.gov →

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Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Follicular lymphoma

Generated from this cancer's standard of care, biomarkers, and pipeline · 17 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example t/BCL2, FLIPI / FLIPI2 / m7-FLIPI, PET-CTstaging and end-of-induction response, POD24, EZH2 mutation), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Classic FL, Follicular large B-cell lymphoma, FL with unusual cytological features.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Limited stage (I-II)

  1. For my situation (limited stage (i-ii)), which of the standard options do you recommend and why?
    Why: Guideline options include: Involved-site radiotherapy 24 Gy (FoRT); rituximab alone or observation in selected cases.
  2. Am I a candidate for Rituximab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Advanced, low burden, asymptomatic

  1. For my situation (advanced, low burden, asymptomatic), which of the standard options do you recommend and why?
    Why: Guideline options include: Watch and wait (no survival penalty), or rituximab monotherapy to delay chemotherapy.
  2. Am I a candidate for Rituximab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Advanced, high burden (GELF criteria)

  1. For my situation (advanced, high burden (gelf criteria)), which of the standard options do you recommend and why?
    Why: Guideline options include: Bendamustine-rituximab or bendamustine-obinutuzumab (GALLIUM), R-CHOP, or lenalidomide-rituximab (RELEVANCE); anti-CD20 maintenance 2 years (PRIMA).
  2. Am I a candidate for Rituximab, Obinutuzumab, Bendamustine or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Relapsed (≥2 lines)

  1. For my situation (relapsed (≥2 lines)), which of the standard options do you recommend and why?
    Why: Guideline options include: Lenalidomide-rituximab (AUGMENT); CD20×CD3 bispecific (mosunetuzumab, epcoritamab); CD19 CAR-T (axi-cel, tisa-cel, liso-cel); zanubrutinib + obinutuzumab; clinical trials.
  2. Am I a candidate for Mosunetuzumab, Epcoritamab, Axicabtagene ciloleucel or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

  1. Are there clinical trials I could join, for example of Epcoritamab, Mosunetuzumab, Odronextamab, Golcadomide?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. Would a second opinion at a high-volume centre change anything, and can you help arrange it?
    Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
  3. What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
    Why: Supportive care improves quality of life and helps patients complete treatment.
  4. I read that “Transformation to DLBCL cannot be predicted or prevented”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Sequencing bispecifics vs CAR-T”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

11
Active surveillanceCAR-T cell therapyCytotoxic chemotherapyEpigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)IMRT / IGRT (modern external beam)Monoclonal antibodiesPET/CTPROTACs & molecular glues (targeted protein degradation)Radio-antibody & radio-ADCSmall-molecule kinase inhibitorsT-cell engagers (bispecific)

targets

8
BCL-2BTK (Bruton tyrosine kinase)CD19CD20CD3CD79bEZH2PIK3CA / PI3K-alpha

drugs

16
ApprovedCAR-T (CD19)
Axicabtagene ciloleucel · Yescarta
Not mapped hereAlkylating agent (nitrogen mustard-purine hybrid)
Bendamustine · Treanda / Bendeka / Belrapzo
WithdrawnIntravenous pan-class I PI3K inhibitor (α/δ predominant)
Copanlisib · Aliqopa
ApprovedBispecific T-cell engager (CD20×CD3)
Epcoritamab · Epkinly
Phase 3Molecular glue degrader (CELMoD, IKZF1/3)
Golcadomide
Not mapped hereSmall-molecule PI3Kδ inhibitor
Idelalisib · Zydelig
ApprovedImmunomodulatory drug (cereblon E3 ligase modulator)
Lenalidomide · Revlimid
ApprovedCAR-T (CD19, defined CD4:CD8)
Lisocabtagene maraleucel · Breyanzi
ApprovedBispecific T-cell engager (CD20×CD3)
Mosunetuzumab · Lunsumio
ApprovedMonoclonal antibody (anti-CD20, glycoengineered type II)
Obinutuzumab · Gazyva
ApprovedBispecific T-cell engager (CD20×CD3)
Odronextamab · Lynozyfic (EU: Ordspono)
ApprovedMonoclonal antibody (anti-CD20, chimeric)
Rituximab · Rituxan / MabThera (and biosimilars)
WithdrawnSmall-molecule EZH2 inhibitor
Tazemetostat · Tazverik
ApprovedCAR-T (CD19)
Tisagenlecleucel · Kymriah
WithdrawnOral PI3Kδ / CK1ε inhibitor
Umbralisib · Ukoniq
ApprovedSmall-molecule covalent BTK inhibitor (second generation)
Zanubrutinib · Brukinsa

companies

10
AbbVie (incl. ImmunoGen, Capstan)BayerBeOne Medicines (formerly BeiGene)Bristol Myers SquibbGenmabGilead Sciences (incl. Kite)IpsenNovartisRegeneronRoche / Genentech

institutions

3
Fred & Pamela Buffett Cancer CenterThe Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research InstituteWilmot Cancer Institute, University of Rochester

pathways

2
Complement in cancerIntrinsic apoptosis (BCL-2 family)

terms

3
Deauville five-point scaleHistologic transformationLugano classification / Ann Arbor staging

collections

2
Leukemia & Lymphoma Society (LLS)Lymphoma Research Foundation (LRF)

key papers

2
EPCORE NHL-1: epcoritamab, a subcutaneous CD20 x CD3 bispecific, in relapsed large B-cell lymphoma including after CAR-TZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma

Key papers

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translationalJournal of Clinical Oncology 2023changed practice
EPCORE NHL-1: epcoritamab, a subcutaneous CD20 x CD3 bispecific, in relapsed large B-cell lymphoma including after CAR-T

CD20 x CD3 bispecifics gave patients whose lymphoma has failed CAR-T, or who cannot access it, an effective off-the-shelf treatment that can be started within days. Epcoritamab and glofitamab are now standard third-line options and are moving into earlier lines and combinations. They do not yet replace CAR-T, whose remissions appear more durable.

translationalNew England Journal of Medicine 2017changed practice
ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma

ZUMA-1 showed that CAR-T can cure a meaningful fraction of adults whose aggressive lymphoma no longer responds to chemotherapy, a group with a historical median survival of about six months (SCHOLAR-1). Axi-cel became the first CAR-T approved for lymphoma and later the first to beat standard second-line therapy in ZUMA-7. The comparatively high neurotoxicity of CD28-costimulated products was also first characterised here.

Latest papers

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Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Follicular lymphoma" OR ABSTRACT:"Follicular lymphoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Follicular lymphoma, not a curated reading list.

Connected

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technologies

7
Active surveillanceCAR-T cell therapyIMRT / IGRT (modern external beam)Monoclonal antibodiesPET/CTRadio-antibody & radio-ADCT-cell engagers (bispecific)

targets

7
BCL-2BTK (Bruton tyrosine kinase)CD19CD20CD3CD79bEZH2

drugs

16
ApprovedCAR-T (CD19)
Axicabtagene ciloleucel · Yescarta
Not mapped hereAlkylating agent (nitrogen mustard-purine hybrid)
Bendamustine · Treanda / Bendeka / Belrapzo
WithdrawnIntravenous pan-class I PI3K inhibitor (α/δ predominant)
Copanlisib · Aliqopa
ApprovedBispecific T-cell engager (CD20×CD3)
Epcoritamab · Epkinly
Phase 3Molecular glue degrader (CELMoD, IKZF1/3)
Golcadomide
Not mapped hereSmall-molecule PI3Kδ inhibitor
Idelalisib · Zydelig
ApprovedImmunomodulatory drug (cereblon E3 ligase modulator)
Lenalidomide · Revlimid
ApprovedCAR-T (CD19, defined CD4:CD8)
Lisocabtagene maraleucel · Breyanzi
ApprovedBispecific T-cell engager (CD20×CD3)
Mosunetuzumab · Lunsumio
ApprovedMonoclonal antibody (anti-CD20, glycoengineered type II)
Obinutuzumab · Gazyva
ApprovedBispecific T-cell engager (CD20×CD3)
Odronextamab · Lynozyfic (EU: Ordspono)
ApprovedMonoclonal antibody (anti-CD20, chimeric)
Rituximab · Rituxan / MabThera (and biosimilars)
WithdrawnSmall-molecule EZH2 inhibitor
Tazemetostat · Tazverik
ApprovedCAR-T (CD19)
Tisagenlecleucel · Kymriah
WithdrawnOral PI3Kδ / CK1ε inhibitor
Umbralisib · Ukoniq
ApprovedSmall-molecule covalent BTK inhibitor (second generation)
Zanubrutinib · Brukinsa

companies

6
AbbVie (incl. ImmunoGen, Capstan)BeOne Medicines (formerly BeiGene)GenmabGilead Sciences (incl. Kite)RegeneronRoche / Genentech

institutions

3
Fred & Pamela Buffett Cancer CenterThe Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research InstituteWilmot Cancer Institute, University of Rochester

pathways

2
Complement in cancerIntrinsic apoptosis (BCL-2 family)

terms

3
Deauville five-point scaleHistologic transformationLugano classification / Ann Arbor staging

collections

2
Leukemia & Lymphoma Society (LLS)Lymphoma Research Foundation (LRF)

key papers

2
EPCORE NHL-1: epcoritamab, a subcutaneous CD20 x CD3 bispecific, in relapsed large B-cell lymphoma including after CAR-TZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma